Eric O. Feigl
The Feigl laboratory is best known for research on the regulation of coronary blood flow which has redundant neural and local metabolic control mechanisms. The challenge has been to separate the autonomic neural feed – forward control from the feedback local metabolic control related to myocardial oxygen consumption. Graphs of coronary venous oxygen tension vs. myocardial oxygen consumption were frequently used to reveal the balance between oxygen supply via coronary blood flow, and myocardial oxygen consumption.
Feed – forward control via parasympathetic cholinergic vasodilation was directly demonstrated by vagal stimulation and was shown to be mediated by nitric oxide. Reflex parasympathetic vasodilation was elucidated in carotid sinus baroreceptor, carotid body chemoreceptor, and Bezold – Jarisch reflexes. Sympathetic feed – forward vasodilation mediated by beta adrenoceptors was demonstrated to be an important component of exercise coronary hyperemia. Paradoxically, there was also a simultaneous alpha adrenoceptor mediated vasoconstrictor effect with sympathetic activation during exercise. The alpha vasoconstriction modestly limited total coronary blood flow, but had the beneficial effect of maintaining flow to the vulnerable subendocardium during exercise when heart rate, myocardial oxygen consumption, and coronary flow were greatly elevated. The mechanism was that the alpha mediated effect reduced the capacitance of vessels penetrating the left ventricular wall, thus decreasing wasteful retrograde flow during systole and allowing better flow to the distal subendocardium during diastole.
Over three decades many laboratories have tested Robert Berne’s adenosine hypothesis of local metabolic feedback control of coronary blood flow. The Feigl laboratory contributed several papers, culminating with a study where a new method was developed to determine myocardial interstitial adenosine concentration in the presence of adenosine receptor blockade during exercise. The accepted conclusion is that adenosine is a pathophysiological vasodilator during myocardial hypoxia or ischemia, but not a physiological controller during normal exercise.
Recent research is based on the work of Mary Ellsworth et.al. who demonstrated that when red blood cells are in a low oxygen tension environment, and oxyhemoglobin saturation is low, the red cells release a small amount of ATP. The new hypothesis for feedback control is that ATP and its break down products ADP and AMP act on endothelial purinergic receptors in coronary veins to initiate a conducted vasodilator signal to upstream arterioles. The red cells in the coronary veins act as the sensors for a feedback controller that adjusts oxygen delivery via coronary blood flow to balance myocardial oxygen metabolism during exercise.
Eric Feigl was born in Iowa City, Iowa and grew up in Minneapolis, Minnesota. He is the son of a famous logical positivist philosopher of science, Herbert Feigl of the Vienna Circle. Eric graduated from the University of Minnesota Medical School and interned at Philadelphia General Hospital. He had postdoctoral training at: the University of Pennsylvania (with Lyle Peterson) , the University of Gothenburg, Sweden (with Bjorn Folkow) , and the National Heart Institute (with Donald Fry). Initially he was an assistant professor at the University of Pennsylvania, and now is a professor of Physiology and Biophysics at the University of Washington, Seattle. Dr. Feigl’s honors include the Katz Prize from the American Heart Association, the Outstanding Research Award of the International Society for Heart Research, the Wiggers Award, and the Berne Award of the American Physiological Society.